The isolation of genes involved in human cancer development is critical for uncovering the molecular basis of cancer. One theory of cancer development holds that there are tumor suppressor genes in all normal cells which, when they become non-functional due to mutations, cause neoplastic development (Knudsen et al., Cancer Res. 45:1482, 1985). Evidence to support this theory has been found in the cases of human retinoblastoma and colorectal tumors (see U.S. Pat. No. 5,330,892 and references cited therein), as well as in connection with breast and ovarian cancers (see U.S. Pat. Nos. 5,693,473 and references cited therein).
More particularly, recurrent deletions on the short arm of human chromosome 8 in cases of liver, breast, lung and prostate cancers have raised the possibility of the presence of tumor suppressor genes in that location. For example, loss on the short arm of chromosome 8 in prostrate cancer (PC) cells was described in Brothman (Cancer Genet. Cytogenet. 95:116-21, 1997). Similar deletions on the short arm of chromosome 8 also have been detected in primary hepatocellular cancer (HCC), non-small cell lung carcinoma (NSCLC) and node-negative breast carcinomas (Isola, Am. J. Pathol. 147:905-11, 1995; and Marchio, et al., Genes Chromo. Canc. 18:59-65, 1997).
While recurrent chromosome 8 deletions in malignant tumors support the relevance of this lesion in carcinogenesis, scientists previously have been unable to identify the tumor suppressor genes involved in such deletions. This lack of knowledge concerning the molecular genetic basis of HCC, and other cancers associated with chromosome 8 deletions, has hampered efforts to diagnose the predisposition to such diseases and to develop more effective treatments aimed at curing genetic deficiencies.
Therefore, it is an object of the present invention to provide a human cDNA molecule corresponding to a previously unknown gene located on the short arm of chromosome 8, the deletion of which appears to be closely associated with the development of HCC and other cancers. The cloning and sequencing of such a cDNA molecule enables new and improved methods of diagnosis and treatment of such diseases.